Enhancing Viability in Static and Perfused 3D Tissue Constructs Using Sacrificial Gelatin Microparticles.

Area of Science:

• Biomaterials Science
• Tissue Engineering
• 3D Bioprinting

Background:

• Engineered tissues face limitations in nutrient delivery to cells deep within constructs, hindering viability.
• Current methods struggle to support cell survival beyond approximately 200 μm due to diffusion constraints.

Purpose of the Study:

• To enhance nutrient diffusion and cell viability in engineered tissues by creating a microporous microenvironment.
• To investigate the use of gelatin microparticles and the FRESH 3D bioprinting technique for scaffold fabrication.
• To assess the impact of scaffold porosity and perfusion on nutrient transport and cell survival in larger constructs.

Main Methods:

• Utilized the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) 3D bioprinting technique.
• Incorporated gelatin microparticles as a thermoresponsive porogen within collagen scaffolds to create interconnected pores.
• Fabricated scaffolds with varying porosity levels and integrated vascular-like channels, applying perfusion for nutrient delivery.

Main Results:

• Scaffolds with 75% porosity significantly increased diffusion rates and cell viability, surpassing the 200 μm limit.
• The combination of microporosity and perfusion enhanced nutrient transport and cell survival in larger engineered tissues.
• Demonstrated a method to create thicker tissues without necrotic regions, addressing a key challenge in tissue engineering.

Conclusions:

• Optimizing scaffold microporosity and perfusion is crucial for overcoming nutrient diffusion limitations in tissue engineering.
• This approach offers a promising strategy for developing thicker, viable engineered tissues at clinically relevant scales.
• The findings pave the way for scalable tissue engineering applications by bridging tissue formation and vascularization processes.